Table 1 List of anti-cancer natural compounds from Chinese herbal medicines

Curcumin

Curcuma longa, Curcuma zedoaria, Acorus calamus L.

Bladder cancer; breast cancer; cervical cancer; colorectal cancer; esophageal squamous cell carcinoma; gastrointestinal cancer; glioma; hepatocellular carcinoma; laryngeal cancer; lung cancer; leukemia; liver cancer; mesothelioma; neuroblastoma; oral squamous cell carcinoma; pancreatic cancer; prostate cancer; renal carcinoma; retinoblastoma

T24, RT4, MDA-MB-231, HeLa, SiHa, HCT-116, HT-29, RKO, HCT-15, DLD-1, EC1, EC9706, KYSE450, TE13, AGS, U87, T98G, HepG2, Tu212, A549, H1299, H460, H292, NCI-H520, NCI-H1373, NCI-H2170, K562, HL-60, PLC/PRF5, WRL68, Huh7, KMCH, RN5, N2a, SCC-25, Patu8988, Panc-1, C4-2, PC-3, LNCaP, VCaP, Caki, O-Rb50, Y79

BxPC-3-GemR xenograft mice; C4-2 xenograft mice; PC-3 xenograft mice; RN5 xenograft mice; U87 xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; induces cell cycle arrest; inhibits cell viability; pro-apoptosis

Activates caspase-3, -9, PARP; Down-regulates Akt, Bcl-2, Bcl-xL, CTGF, cyclin D1, cyclin E1, ERK1/2, EZH2, FoxM1, GLI1, ITGA5, Jak1, JNK, MMP-2, Mcl-1, NF-κB, Notch1, p15, p16, p62, p70S6 K, ROCK1, RhoA, SHH, SSAT, STAT1, STAT3, Suz12, TROP2, vimentin, WT1, XIAP, YAP/TAZ; Enhances cytochrome c release, ROS accumulation; Inhibits CDK2 activity, PI3K/Akt/mTOR, SHH/GLI1, STAT3, TGF-β pathways; Up-regulates AIF, Bax, Bex-1, -2, -3, -4, -6, HIF-1α, microRNA-15a, microRNA-16-1, microRNA-99a, p21, p53, p73, PKD1, SMOX

0–5 μM; 0–15 μM; 0–16 μM; 0–20 μM; 0–25 μM; 0–40 μM; 0–50 μM; 0–125 μM; 10–40 μM; 15, 25 μM; 25 μM; 30 μM; 0–6 μg/ml; 5 mg/kg; 60 mg/kg; 200 mg/kg; 500 mg/kg; 25 μg/mouse

Gemcitabine; NVP-BEZ235; α-Tomatine

[12, 21, 795,796,797,798,799,800,801,802,803,804,805,806,807,808,809,810,811,812,813,814]

EGCG

Camellia sinensis

Biliary tract cancer; bladder cancer; breast cancer; cervical cancer; colorectal cancer; gallbladder cancer; gastric cancer; glioblastoma; head and neck cancer; lung cancer; nasopharyngeal carcinoma; NSCLC; oral cancer; pancreatic cancer; pheochromocytoma; prostate cancer; skin cancer

BDC, CCSW-1, EGI-1, SkChA-1, TFK-1, SW-780, MCF-7, 4T1, T47D, MDA-MB-231, MDA-MB-436, SUM-149, SUM-190, HeLa, DLD-1, HT-29, HCT-116, GBC, MzChA-1, MzChA-2, SGC-7901/FU, MGC-803/FU, AGS, C6, U251, SHG-44, U87, K3, K4, K5, CL1-5, CL1-0, TW01, TW06, NCI-H1299, A549, H460, SCC-9, MIA PaCa-2, Panc-1, PC-12, BCaPT1, BCaPT10, BCaPM-T10, LNCaP, A431, SCC13

4T1 xenograft mice; A549 xenograft mice; BCaPT10 xenograft mice; BCaPM-T10 xenograft mice; CL1-5 xenograft mice; Oral squamous cell carcinoma xenograft mice; PC-12 xenograft mice; SCG-7901/FU xenograft mice; SSC-9 xenograft mice; SUM-149 xenograft mice; SW-780 xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; induces autophagy, cell cycle arrest; inhibits cell viability, epithelial–mesenchymal transition; pro-apoptosis

Activates caspase-3, -7, PARP; Down-regulates ABCG2, Akt, AXL, Bcl-2, Bcl-xL, E-cadherin, β-catenin, CDK2, CDK4, COX-2, CTTN, cyclin B1, cyclin D1, cyclin D2, cyclin D3, DNMT1, EGFR, ERα, ERK1/2, FAK, FN1, GSK3β, HDAC1, HER2, HSP90, IKKα, JNK, MDR-1, MGMT, MMP-2, MMP-9, NANOG, NF-κB, Notch, Oct-4, u-PA, paxillin, P-gp, PI3K, Raf-1, Snail, SOX2, Sp1, Src, STAT3, survivin, TFAP2A, Tyro3, VEGF, vimentin; Enhances cytochrome c release, ROS accumulation; Induces mitochondrial depolarization; Inhibits MAPK/ERK, PI3K/Akt pathways; Reduces ATP levels; Represses DNA replication; Up-regulates Bax, CK1α, endostatin, microRNA-16, p21, p53, TIMP-1, TIMP-2

0–20 µM; 0–40 µM; 0–50 µM; 0–100 µM; 0–200 µM; 0–400 μM; 2–100 μM; 10 μM; 20 μM; 25, 50, 100 μM; 40 μM; 50, 100 μM; 80 µM; 0–60 μg/ml; 10 mg/kg; 10–20 mg/kg; 15 mg/kg; 16.5 mg/kg; 20 mg/kg; 25 mg/kg; 25–100 mg/kg; 50 mg/kg; 0.025%, 0.05%; 0.06%

Bleomycin; Cisplatin; Curcumin; Docetaxel; 5-Fluorouracil; Oxaliplatin; Pterostilbene; Temozolomide

[93,94,95, 100, 101, 103, 123,124,125, 815,816,817,818,819,820,821,822,823,824,825,826,827,828,829,830,831,832,833,834]

Berberine

Coptidis cgubebsus Franch., Mahonia bealei (Fort.) Carr., Phellodendron chinense Schneid

Breast cancer; cervical cancer; cholangiocarcinoma; colorectal cancer; endometrial carcinoma; esophageal squamous cancer; gastric cancer; glioblastoma; head and neck cancer; hepatocellular carcinoma; leukemia; lung cancer; medulloblastoma; melanoma; nasopharyngeal carcinoma; oral squamous cell carcinoma; osteosarcoma; ovarian cancer; pancreatic cancer; prostate cancer; skin cancer; uterine leiomyoma

MCF-7, MCF-7/HER2, MCF-7/TAM, MDA-MB157, MDA-MB231, MDA-MB453, BT20, BT549, Hs578T, T47D, SKBR3, BT474, HeLa, SiHa, QBC939, KKU-213, KKU-214, SW-480, SW-620, HT-29, DLD-1; HCT-116, LS174T, LoVo, Eca109, TE13, KYSE-70, EAC, SKGT4, AN3 CA, HEC-1-A, KLE, MGC-803, SGC-7901, AGS, BGC-823, MKN45, U87, U251, U118, SHG-44, FaDu, H22, Hepa1-6, HepG2, Bel-7404, Huh7, WRL68, MHCC97L, K562, A549, B16F10, HONE1, HK1-EBV, CNE-2, KB, U2OS, Panc-1, MIA PaCa-2, LNCaP, DU-145, LAPC-4, PC-3, 22RV1, C4-2B, C42, RM-1, A-431

22RV1 xenograft mice; A2780 xenograft mice; A549 xenograft mice; BGC-823 xenograft mice; Eca109 xenograft mice; H22 xenograft mice; HONE1 xenograft mice; LoVo xenograft mice; LNCaP xenograft mice; MDA-MB-231 xenograft mice; Medulloblastoma xenograft mice; MHCC97L xenograft mice; SGC-7901 xenograft mice; SW-620 xenograft mice; SiHa xenograft mice; U87 xenograft mice

Anti-angiogenesis; anti-proliferation; anti-metastasis; enhances radiosensitivity; induces autophagy, cell cycle arrest; inhibits cell viability, epithelial–mesenchymal transition; pro-apoptosis

Activates caspase-3, -7, -8, -9, PARP; Decreases mitochondrial membrane potential, catalase and superoxide dismutase activities; Down-regulates Akt, AR, Bcl-2, Bcl-xL, Bid, β-catenin, N-cadherin, CDK1, CDK2, CDK4, COX-2, PLA2, cyclin A1, cyclin B1, cyclin D1, cyclin E, DHCR24, DHFR, E2F1, EBNA1, EGFR, EF-Tu, ERK, Ezrin, FAK, FN, HER2, HIF-1α, HMGB1, HNF4α, ITGβ1, Jak2, JNK, Mcl-1, MEK, MMP-1, MMP-2, MMP-9, mTOR, c-Myc, NANOG, NF-κB, iNOS, occludin, Oct-4, p38, p50, p62, p100, p105, p70S6 K, paxillin, u-PA, PCNA, PDK1, PGE₂, PKC-α, PSA, PTEN, PTTG-1, RAD51, b-Raf, c-Raf, Septin-8, Slug, Snail, SOX2, Sp1, Src, STAT3, survivin, UQCRC1, VEGF, vimentin, Wnt5α, ZEBRA; Enhances cytochrome c release, ROS accumulation, SSAT activity; Induces DNA damage; Inhibits Akt/mTOR/p70S6 K/S6, arachidonic acid metabolic, androgen receptor pathways; Reduces NO production; Suppresses Hedgehog signaling pathway; Up-regulates ACC, AIF, AMPKα, Apaf-1, ATF-6, Bad, Bak, Bax, Beclin-1, Bim, E-cadherin, DR5, FasL, FoxO1, FoxO3a, GRP78, HRK, Lig4, MST1, p21, p27, p53, PHLPP2, SSAT, TIMP-2, TRAIL, ULK1

0–10 µM; 0–20 μM; 0–25 μM; 0–40 μM; 0–50 µM; 0–80 μM; 0–90 µM; 0–100 µM; 0–120 µM; 0–150 μM; 0–160 µM; 0–200 µM; 0–250 μM; 0–350 μM; 0–1000 μM; 10–80 μM; 15 µM; 20 μM; 50 μM; 0–1 µg/ml; 0–80 μg/ml; 5 mg/kg; 10 mg/kg; 12.5–50 mg/kg; 20 mg/kg; 50, 100 mg/kg; 50–200 mg/kg; 200 mg/kg; 0.01136 g/kg

Caffeine; Cetuximab; Doxorubicin; Erlotinib; d-limonene; Niraparib; Tamoxifen; Taxol; TRAIL

[139, 140, 144, 145, 147,148,149, 153, 171, 174, 835,836,837,838,839,840,841,842,843,844,845,846,847,848,849,850,851,852,853,854,855,856,857,858,859,860,861,862,863,864,865,866,867,868,869,870]

Artemisinins

Artemisia annua L.

Breast cancer; cervical cancer; colorectal cancer; gallbladder cancer; gastric cancer; glioma; hepatocellular carcinoma; Ishikawa endometrial cancer; lung cancer; neuroblastoma; oral carcinoma; pancreatic cancer

MCF-7, MDA-MB-231, HeLa, HCT-116, SW-480, SW-620, GBC-SD, NOZ, MGC-803, C6, HepG2, Hep3B, SMMC-7721, Ishikawa, A375, A549, ASTC-a-1, H1299, BE(2) -C, SHEP1, SK-N-AS, SK-N-DZ, SCC25, RIN

A549 xenograft mice; BE(2)-C xenograft mice; C6 xenograft mice; GBC-SD xenograft mice; HCT-116 xenograft mice; HepG2 xenograft mice; NOZ xenograft mice

Anti-metastasis; anti-proliferation; induces apoptosis, autophagy, cell cycle arrest; inhibits cell viability

Activates caspase-3, -8, -9, PARP; Decreases mitochondrial membrane potential, MMP activity; Down-regulates Bcl-2, CDK2, CDK4, cyclin D1, cyclin E2, Dvl2, ERK1/2, LRP6, MMP-2, NANOG, Oct-4, p38, p62, SOX2, vimentin, Wnt5α/β; Enhances cytochrome c release, ROS accumulation; Induces DNA damage; Inhibits Wnt/β-catenin signaling pathway; Up-regulates Axin2, Bax, E-cadherin, β-catenin, NKD2, p16, TIMP-2

0–75 μM; 0–160 μM; 0–200 μM; 0–250 μM; 0–400 μM; 0–500 μM; 0–1000 μM; 0–1200 μM; 10–320 μM; 40–160 μM; 0–40 μg/ml; 10 mg/kg; 50 mg/kg; 60 mg/kg; 100 mg/kg

3CA; Halofuginone; Holotransferrin; Resveratrol

[184, 186, 213, 871,872,873,874,875,876,877,878,879,880,881,882,883]

Ginsenoside Rg3

Panax notoginseng (Burk.) F. H. Chen, Panax ginseng, Cinnamomum cassia Presl.

Breast cancer; colorectal cancer; esophageal carcinoma; gallbladder cancer; gastric cancer; glioblastoma; glioma; hepatocellular carcinoma; leukemia; lung cancer; melanoma; multiple myeloma; ovarian cancer; pancreatic cancer; prostate cancer

BT549, MDA-MB-231, MDA-MB-453, CT-26, HCT-116, LoVo, SW-480, SW-620, EC109, KYSE170, TE1, GBC-SD, Mz-ChA-1, QBC939, SGC-7901, U87MG, U87, Hep1-6, HepG2, Lewis, Jurkat, A549, A549/DDP, H23, H1299, A375, C8161, SK-MEL-28, RPMI 8226, SKO-007, U266, A2780, 3AO, SKOV3, AcPC-1, BxPC-3, Panc-1, SW1990, PC-3

A375 xenograft mice; A549 xenograft mice; BxPC-3 xenograft mice; CT-26 xenograft mice; GBC-SD xenograft mice; HCT-116 xenograft mice; Hep1-6 xenograft mice; H23 xenograft mice; Lewis tumor-bearing mice; LoVo xenograft mice; MDA-MB-231 xenograft mice; MCF- 7 xenograft mice; SKOV3 xenograft mice; SW1990 xenograft mice; SW-620 xenograft mice

Anti-angiogenesis; anti-proliferation; anti-metastasis; enhances radiosensitivity; increases cell survival; induces autophagy, cell cycle arrest; inhibits chemotaxis, epithelial–mesenchymal transition; pro-apoptosis

Activates caspase-3, -8, -9, 12, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, AQP1, B7-H1, B7-H3, Bcl-2, Bcl-xL, VE-cadherin, CDK2, COX-2, CXCR4, cyclin D1, cyclin E, DNMT3A, EGFR, EPHA2, ERK, FUT4, HDAC3, HIF-1α, HK2, IAP, JNK, LeY, MMP-2, MMP-9, mTOR, c-Myc, NF-κB, p38, p53, PCNA, PD-L1, PI3K, PKM2, Rb, STAT3, surviving, VEGF; Enhances cytochrome c release, ROS production; Inhibits the Warburg effect, Wnt/β-catenin pathway; Up-regulates Atg-5, Atg-7, Bax, CHOP, IRE1, microRNA-532-3p, p16, p21, p27, p53, PERK

0–10 μM; 0–30 μM; 0–35 μM; 0–60 μM; 0–80 μM; 0–100 μM; 0–150 μM; 0–160 μM; 0–200 μM; 0–400 μM; 0–600 μM; 25 μM; 0–600 ng/ml; 0–80 μg/ml; 0–100 μg/ml; 0–160 μg/ml; 0–200 μg/ml; 40, 80 μg/ml; 50 μg/ml; 80, 160 μg/ml; 80, 160 mg/ml; 3 mg/kg; 5 mg/kg; 5, 10, 20 mg/kg; 6 mg/kg; 7.5–30 mg/kg; 10 mg/kg; 20 mg/kg

Cisplatin; Cyclophosphamide; Erlotinib; 5-Fluorouracil; Oxaliplatin; Paclitaxel

[227, 232,233,234, 236,237,238,239,240,241, 246, 252,253,254,255, 260, 884,885,886,887,888,889,890,891,892,893,894,895,896,897,898,899,900]

Ursolic acid

Vaccinium macrocarpon Ait., Arctostaphylos uva-ursi (L.) Spreng, Rhododendron hymenanthes Makino, Eriobotrya japonica, Rosemarinus officinalis, Calluna vulgaris, Eugenia jambolana, Ocimum sanctum

Bladder cancer; breast cancer; cervical cancer; colorectal cancer; Ehrlick ascites carcinoma; leukemia; liver cancer; lung cancer; melanoma; ovarian cancer; prostate cancer; skin cancer

BIU-87, T24, MDA-MB-231, MCF-7, MCF-7/ADR, HeLa, HCT-8, HCT-116, HT-29, Caco-2, SW-480, SW-620, HCT-15, CO115, HL-60, HL-60/ADR, Jurkat, K562, K562/ADR, U937, HL-60/ADR, Hep3B, Huh7, HA22T, A549, H3255, Calu-6, M4Beu, SKOV3, DU-145, LNCaP, PC-3

12-dimethylbenz[a]anthracene-induced mice; DU-145 xenograft mice; Ehrlich ascites carcinoma xenograft mice; HCT-116 xenograft mice; HCT-15 xenograft mice; U937 xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; enhances chemosensitivity; induces apoptosis, autophagy, cell cycle arrest; inhibits MDR

Activates caspase-3, -7, -8, -9, Fas receptor, PARP; Decreases mitochrondrial membrane potential; Down-regulates AEG-1, Akt, Bcl-2, Bcl-xL, Bid, β-catenin, CD31, cyclin D1, EGFR, ERK, cFLIP, FN, HIF-1α, cIAP-1, ICAM-1, IκBα, IKKα/β, IL-8, Jak2, Ki-67, Mcl-1, MMP-2, MMP-9, NF-κB, iNOS, p65, u-PA, P-gp, S6 K, Src, STAT3, survivin, mTOR, TNF-α, VEGF, Wnt5α/β, XIAP; Enhances cytochrome c release, PGE₂ levels, ROS production; Inhibits NO production; Up-regulates ACC, AMPK, ASK1, Bax, CHOP, DR4, DR5, eIF2α, GRP78, GSK3β, IL-12, JNK, c-Jun, NADPH, p21, p52, p53, PERK

0–4 μM; 0–16 μM; 0–17.5 μM; 0–20 μM; 0–40 μM; 0–50 μM; 0–80 μM; 0–100 μM; 4 μM; 20 μM; 0–400 μg/ml; 10 mg/kg; 25–100 mg/kg; 50 mg/kg; 75 mg/kg; 250 mg/kg; 2 μmol/mouse

Capecitabine; 5-Fluorouracil; Oxaliplatin; Resveratrol; TRAIL

[274, 276, 281, 283,284,285,286,287,288,289, 293, 901,902,903,904,905,906,907]

Silibinin

Silybum marianum L. Gaertn

Breast cancer; colorectal cancer; epidermoid carcinoma; glioblastoma; hepatocellular carcinoma; osteosarcoma; pancreatic cancer; prostate cancer; renal carcinoma; thyroid cancer

BT-20, MCF-7, MDA-MB-231, MDA-MB-468, SKBR3, T47D, AsPC-1, BxPC-3, Panc-1, HT-29, HCT-116, LoVo, SW-480, Caco-2, A-431, LN18, SNB19, U87MG, Hep3B, HepG2, SK-Hep-1, SaOS2, PC-3, 769-P, 786-O, ACHN, OS-RC-2, SW839, Caki, TPC-1

786-O xenograft mice; Azoxymethane-induced rats; Diethylnitrosamine-induced mice

Anti-metastasis; anti-proliferation; induces apoptosis, autophagy, cell cycle arrest; inhibits cell viability

Activates caspase-3, -8, -9, PARP; Down-regulates Akt, Bcl-2, EGFR, ERK, GLI1, IL-1β, FN, MMP-2, MMP-7, MMP-9, NF-κB, iNOS, PLA2, TNF-α, mTOR; Enhances CYP2E1 activity, cytochrome c release, ROS production; Up-regulates AIF, Bax, Bid, calpain, EGR1, ICAD, NAG-1, PTEN

0–75 μM; 0–100 μM; 0–200 μM; 0–300 μM; 0–800 μM; 25, 50 μM; 120 μM; 125 μM; 200 mg/kg; 300 mg/kg; 0.5%

Curcumin; luteolin

[318, 319, 329,330,331, 334, 342,343,344,345, 357, 358, 908,909,910]

Emodin

Rheum palmatum, Polygonum cuspidatum, Polygonum multiflorum, Cassia obtusifolia

Bladder cancer; breast cancer; colorectal cancer; gallbladder cancer; gastric cancer; hepatocellular carcinoma; lung cancer; nasopharyngeal carcinoma; oral carcinogenesis; ovarian cancer; pancreatic cancer; prostate cancer

MBT2, T24, TSGH8301, 4T1, EO771, MCF-7, MDA-MB-231, MDA-MB-435, MDA-MB-453, HCT-116, LoVo, LS1034, SGC-996, MKN45, C3A, Hep3B, HepG2, PLC/PRF/5, SMMC-7721, A549, CNE-2Z, A2780, SKOV3, AsPC-1, BxPC-3, Panc-1, SW1990, SW1990/GZ, PC-3

4T1 xenograft mice; 7,12-dimethyl benz(a)anthracene-induced golden Syrian hamsters; EO771 xenograft mice; HCCLM3 tumor-bearing mice; LS1034 xenograft mice; MDA-MB-231 xenograft mice; SGC-996 xenograft mice; SKOV3 xenograft mice; SW1990 xenograft mice; T24 xenograft mice

Anti-metastasis; anti-proliferation; induces apoptosis, autophagy, cell cycle arrest; inhibits cell viability, epithelial-mesenchymal transition

Activates caspase-3, -9, PARP, chloride currents; Decreases mitochondrial membrane potential; Down-regulates Akt, Bcl-2, Bcl-xL, Bim-1, β-catenin, CDK1, CSF1, CSF2, CXCL12, CXCR4, cyclin D1, ERα, ERK, FABP4, bFGF, HBP17, HER2, ILK, Jagged1, Jak1, Jak2, Ki-67, Mcl-1, MCP-1, MMP-2, MMP-9, MRP1, NF-κB, p38, p62, u-PA, u-PAR, Slug, Snail, Src, STAT3, survivin, Thy-1, VEGF, vimentin, XIAP, ZEB1; Enhances Ca²⁺ levels, cytochrome c release, ROS production; Up-regulates AIF, Bax, Beclin-1, E-cadherin, GSK3β, microRNA-34, Notch1, SHP-1

0–10 μM; 0–40 μM; 0–50 μM; 0–60 μM; 0–80 μM; 0–100 μM; 0–250 μM; 0–320 μM; 0–1000 μM; 20 μM; 20–80 μM; 40 μM; 0.05 mM; 40 mg/ml; 20, 40 mg/kg; 20, 50 mg/kg; 25, 50 mg/kg; 40 mg/kg; 50 mg/kg

Cisplatin; curcumin; 5-fluorouracil; gemcitabine

[64, 367,368,369,370,371,372,373,374,375,376,377,378, 380, 382, 383, 385, 389, 394, 395, 402, 403, 405, 911]

Triptolide

Tripterygium wilfordii Hook. F.

Bladder cancer; breast cancer; colorectal cancer; endometrial carcinoma; liver cancer; lung cancer; lymphoma; melanoma; myeloma; nasopharyngeal carcinoma; neuroblastoma; osteosarcoma; ovarian cancer; oral cancer; pancreatic cancer; prostate cancer

UMUC3, MDA-MB-231, MCF-7, DLD-1, HCT-116, HEC-1B, MHCC-97H, HepaRG, HepG2, H460, H358, A549, A549/Taxol, HTB182, BEAS-2B, H1299, NCI-H2009, NCI-H460, Jurkat, Molt-3, Raji, NAMALWA, Daudi, B16F10, HS-sultan, IM9, RPMI 8226, U266, CNE, MG63, BE(2)-C, SH-SY5Y, SAOS2, U2OS, SKOV3, SKOV3/DDP, A2780, SAS, Panc-1, AsPC-1, SW1990, BxPC-3, LNCaP, PC-3, DU-145

3LL xenograft mice; A549 xenograft mice; AsPC-1 xenograft mice; BE(2)-C xenograft mice; CNE xenograft mice; Daudi xenograft mice; H358 xenograft mice; H460 xenograft mice; HEC-1B xenograft mice; Jurkat xenograft mice; MHCC-97H xenograft mice; SAS + U937 xenograft mice; SKOV3/DDP xenograft mice; SW1990 xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; enhances radiosensitivity; induces autophagy, cell cycle arrest; inhibits cell viability; pro-apoptosis

Activates caspase-3, -7, -8, -9, GSK3β, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, AR, BCAR1, Bcl-2, β-catenin, Cav-1, CD147, CDK2, CHK1, COX IV, CXCR4, cyclin A1, ERK, ETS2, FAK, c-FLIP, GRB2, HIF-1α, HSF1, HSP70, IκBα, ITGβ1, ITGαVβ6, JMJD3, JMJD2B, NK, p38 MAPK, Mcl-1, MKP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-14, MMP-19, c–Myc, NF-κB, iNOS, Nrf2, p65, PCNA, PI3K, PYK2, ROCK1, RhoA, Slug, Snail, SOS1, Src, survivin, mTOR, Twist, UTX, VEGF, vimentin, ZEB1; Enhances Ca²⁺ levels, cytochrome c release, ROS production; Inhibits Wnt/β-Catenin pathway; Up-regulates ATM, Bax, Beclin-1, E-cadherin, cathepsin B, Fas, DKK1, DR5, ENY2, FADD, FRZB, GSK3β, IL-2, γ-H2AX, LMP, LSD1, p53, PPARγ, PTEN, SFRP1, SIRT3, Smac, SUV39H1, TNF-α, Wnt3α

0–10 nM; 0–40 nM; 0–50 nM; 0–80 nM; 0–100 nM; 0–160 nM; 0–200 nM; 0–300 nM; 0–320 nM; 0–400 nM; 0–500 nM; 0–0.1 μM; 0–25 μM; 0–150 μM; 0–200 μM; 10 nM; 50, 72 nM; 100 nM; 0–8 ng/ml; 0–36 ng/ml; 0–50 ng/ml; 0–400 ng/ml; 5, 10 ng/ml; 5–160 ng/ml; 8 ng/ml; 250 μg/kg; 0–0.8 mg/kg; 0.04–0.36 mg/kg; 0.075 mg/kg; 0.15 mg/kg; 0.25 mg/kg; 0.4 mg/kg; 1 mg/kg; 1.5 mg/kg; 2–4 μg/mouse

Cisplatin; epirubicin; 5-fluorouracil; gemcitabine; hydroxycamptothecin

[408, 410, 411, 414, 415, 417, 419, 422, 423, 425,426,427, 429, 431,432,433,434, 438, 444, 446, 453, 454, 912,913,914,915,916,917,918,919,920,921,922,923,924,925]

Cucurbitacin B

Bryonia, Cucumis, Cucurbita and Lepidium sativum

Breast cancer; cervical cancer; hepatocellular carcinoma; lung cancer; neuroblastoma; prostate cancer

4T1, HCC1937, MCF-7, MCF-7/ADR, MDA-MB-231, MDA-MB-436, SKBR-3, HeLa, T47D, SK-Hep1, Hep3B, HepG2, Bel-7402, Bel-7402/5-Fu, A549, H1299, H23; SH-SY5Y; LNCaP, PC-3

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mice; 4T-1 xenograft mice; Bel-7402 xenograft mice; MDA-MB-231 xenograft mice; NNK-induced mice; PC-3 xenograft mice

Anti-angiogenesis; Anti-metastasis; Anti-proliferation; Inducing apoptosis, cell cycle arrest; Inhibits epithelial-mesenchymal transition

Activates caspase-3, -8, -9, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, ACLY, BCAR1, Bcl-2, β-catenin, CD31, CDK1, CIP2A, cyclin B1, cyclin D1, EGFR, ERK, FAK, galectin-3, GSK3β, HER2, HIF-1α, ILK1, ITGA6, ITGB4, Jak2, MMP-2, MMP-9, MRP1, c-Myc, nucleophosmin, P-gp, paxillin, RhoA, ROCK1, STAT3, Src, survivin, TACE, TCF1, mTOR, Twist, VEGF, VEGFR2, Wnt3; Enhances cytochrome c release, PP2A activity, ROS production; Inhibits Wnt/β-catenin pathway; Up-regulates ATM, Bax, Bim, E-cadherin, CDC25C, CHK1, γ-H2AX, JNK, p21, p53

0–100 nM; 0–200 nM; 0–1000 nM; 0.1–1000 nM; 0–0.1 μM; 0–1 μM; 0–1.6 μM; 0–30 μM; 0–100 μM; 0–128 μM; 0.02– 62.5 μM; 0–100 μg/ml; 0.1–100 μg/ml; 0.1, 0.2 mg/kg; 0.1, 0.25 mg/kg; 0.5, 1 mg/kg; 1, 5 mg/kg; 2 mg/kg; 10 mg/kg; 0.1 μmol/mouse

Curcumin; docetaxel; gefitinib; gemcitabine

[452, 460,461,462, 472,473,474,475, 485, 499, 926,927,928,929,930,931]

Tanshinone IIA

Salvia miltiorrhiza Bunge

Breast cancer; bladder cancer; cervical cancer; colorectal cancer; esophageal carcinoma; gastric cancer; NSCLC; osteosarcoma; oral squamous carcinoma

BT-20, 5637, BFTC 905, T24, HeLa, C33 A, HCT-116, COLO-205, LoVo, HT-29, SW-620, Eca109, SGC-7901, MKN45, A549, H596, H1299, Calu-1, H460, 143B, SCC090

HT-29 xenograft mice; MKN45 xenograft mice; SGC-7901 xenograft mice; 143B xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; enhances chemosensitivity, radiosensitivity; induces autophagy, cell cycle arrest; inhibits cell viability, epithelial–mesenchymal transition; pro-apoptosis

Activates caspase-3, -8, -9, -12, PARP; Down-regulates ALDH1, Bcl-2, BIP, N-cadherin, β-catenin, CD31, COX-2, CTGF, FoxM1, HIF-1α, Ki-67, LEF1, MCP-1, Mfn-1, Mfn-2, MMP-2, MMP-9, c-Myc, NANOG, Opa-1, p65, PCNA, Slug, Snail, STAT3, survivin, TCF3, VEGF, vimentin, YAP; Enhances cytochrome c release, ROS accumulation; Reduces mitochondrial membrane potential; Up-regulates ATF-4, Bax, Bak, Bad, E-cadherin, CHOP, Drp-1, DR5, GRP78, p21

0–8 μM; 0–20 µM; 0–40 µM; 0–60 µM; 0–80 μM; 0–100 µM; 0–54.4 μM; 0–20 ng/ml; 0–4 µg/ml; 0–8 μg/ml; 0–18 µg/ml; 0–60 µg/ml; 1 mg/kg; 10, 30 mg/kg; 20 mg/kg

Adriamycin 5-fluorouracil; TRAIL

[514, 515, 517, 519, 523, 531, 539, 932,933,934,935]

Oridonin

Rabdosia rubescens (Hemsl.) Hara

Breast cancer; cervical cancer; colorectal cancer; esophageal cancer; gastric cancer; hepatocellular carcinoma; laryngeal; leukemia; liver cancer; lung cancer; melanoma; multiple myeloma; neuroblastoma; oral squamous carcinoma; osteosarcoma; ovarian cancer; pancreatic cancer; prostate cancer; uveal melanoma

4T1, MCF-7, MDA‑MB‑231, SW-48, SW-480, SW-620, SW-1116, HeLa, LoVo, HCT-116, HCT-15, COLO-205, RKO, EC9706, KYSE-30, KYSE-150, SGC-7901, AGS, HepG2, Huh6, MHCC97-H HCC, Hep-2, K562, K562/ADR, HL-60, HL-60/ADR, MV4-11/DDP, MOLM-13/DDP, A549, SHSY-5Y, SK-N-MC, LP-1, SCC-25, HSC-3, HSC-4, MG63, U2OS, HOS, Saos-2, 143B, WSU-HN4, WSU-HN6, CAL27, SKOV3, BxPC-3, PC-3, LNCaP, DU-145, RM-1, MUM2B, OCM-1

143B xenograft mice; 4T1 xenograft mice; HCT-116 xenograft mice; HepG2 xenograft mice and zebrafish; HL-60 xenograft mice; HOS xenograft mice; K562 xenograft mice; KYSE-150 xenograft mice; LoVo xenograft mice; MV4-11/DDP xenograft mice; RM-1 xenograft mice; SCC-25 xenograft mice; SHSY-5Y xenograft mice; SW-480 xenograft mice; WSU-HN6 xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; induces apoptosis, autophagy, cell cycle arrest, epithelial–mesenchymal transition

Activates caspase-3, -8, -9, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, AMPK, AP-1, Bcl-2, Bcl-xL, N-cadherin, CD31, CD44, CDC25C, CDK1, CDK2, Claudin 1, Claudin 4, Claudin 7, α-CPI, cyclin B1, cyclin D1, cyclin E, DHFR, EGFR, ERK, GLUT-1, GSK3β, HO-1, ICAD, Mcl-1, MCT1, MDM2, MMP-2, MMP-9, c-Myc, NF-κB, Notch, Nrf2, NQO1, p38, p62, PCNA, PI3K, Rac2, Raf, Ras, SERTAD1, Slug, Smad, Snail, Stathmin, SREBP1, mTOR, vimentin; Enhances cytochrome c release, intracellular Ca²⁺ levels, ROS production; Inhibits TrxR activity; Up-regulates AIF, ASK1, ATM, Bad, Bax, Beclin-1, Bim, BMP7, E-cadherin, CHK2, CHOP, CKS2, eIF2α, FADD, GADD45AQ, GRP78, γ-H2AX, HERC5, HSP90, IRE1, JNK, p21, p53, PERK, PPARγ, RECQL4, SFN, PTEN

0–1000 nM; 0–1.5 μM; 0–4 μM; 0–9 μM; 0–12 μM; 0–15 μM; 0–20 μM; 0–25 μM; 0–30 μM; 0–32 μM; 0–40 μM; 0–50 μM; 0–60 μM; 0–64 μM; 0–80 μM; 0–100 μM; 0–160 μM; 36 μM; 0–10 mM; 0–64 μg/ml; 5–30 μg/ml; 1.875, 7.5 mg/ml; 1 mg/kg; 2–8 mg/kg; 2.5–10 mg/kg; 5, 10 mg/kg; 5–10 mg/kg; 5–15 mg/kg; 7.5–30 mg/kg; 10 mg/kg; 10, 20 mg/kg; 15 mg/kg; 30 mg/kg; 50, 100 mg/kg

Cisplatin; NVP-BEZ235; valproic acid

[544,545,546,547,548,549,550,551,552,553,554,555,556, 558,559,560,561,562,563,564,565,566,567, 573,574,575,576, 578, 579, 936,937,938,939,940,941,942,943,944,945,946]

Shikonin

Lithospermum erythrorhizon, Arnebia euchroma, Arnebia guttata

Breast cancer; cervical cancer; colorectal cancer; gallbladder cancer; gastric cancer; glioblastoma multiforme; glioma; hepatocellular carcinoma; leukemia; lung cancer; NSCLC; renal carcinoma; pancreatic cancer; thyroid cancer

MCF-7, MDA-MB-231, SKBR3, HeLa, HCT-116, HT-29, SNU-407, SW-1116, SW-680, SW-620, NOZ, BGC-823, SGC-7901, Primary glioblastoma stem cells, C6, SHG-44, U87, U251, SMMC-7721, NB4, Calu-6, H358, HCC-2279, NCI-H15, NCI-H460, NCI-H1229, NCI-H1437, NCI-H1703, A549, 789-O, Capan-1, Suit-2, 8305C, 8505C, BCPAP, C643, FTC133, IHH4, K1, TPC1

A549 xenograft mice; Glioblastoma stem cell xenograft mice; HCT-116 xenograft mice; NOZ xenograft mice; SGC-7901 xenograft mice

Anti-metastasis; anti-proliferation; enhances chemosensitivity; induces apoptosis, cell cycle arrest, necroptosis

Activates caspases-3, -8, -9, -12, PARP, JNK/c-Jun, p38 MAPK, PERK/elF2α/CHOP, pathways; Decreases mitochondrial membrane potential; Down-regulates Akt, Bcl-2, CDK4, cyclin D1, FoxO3a, ICBP90, ITGβ1, MDM2, MMP-9, c-Myc, RIPK1; Elevates intracellular Ca²⁺ and ROS levels; Enhances Ca²⁺ and K⁺ efflux; Inhibits ERK pathway, PKM2 activity; Promotes RIP1/RIP3 necrosome formation; Up-regulates Bax, Bim, Cbl-b, CHOP, cytochrome c, EGR1, eIF2α, GRP78, IRE1α, p16, p21, p53, p73, PERK, RIP1, RIP3

0–2 μM; 0–4 μM; 0–5 μM; 0–6 μM; 0–10 μM; 0–20 μM; 0–50 μM; 0.1–0.4 μM; 1 μM; 2 μM; 20 mg/kg; 2 mg/kg

Cisplatin; 5-fluorouracil; oxaliplatin

[593, 595, 600, 603, 607, 611, 614, 615, 617, 620, 636, 947,948,949,950,951,952]

Gambogic acid

G. hanburyi, G. Morella

Breast cancer; colorectal cancer; glioma; hepatocellular carcinoma; NSCLC; osteosarcoma; ovarian cancer; pancreatic cancer; prostate cancer; renal carcinoma

4T1, MCF-7, MDA-MB-231, HCT-15, HCT-15R, HCT-116, HT-29, SW-480, SW-620, LoVo/L-OHP, LoVo/L-OHP/GA, T98G, Hep3B, Huh7, A549, A549/DDP, SPC-A-1, MG63, SKOV3, BxPC-3, Capan-1, Capan-2, Colo-357, MIA PaCa-2, Panc-1, Suit-007, Suit-2, SW1990, B6WT, DU-145, LAPC-4, LNCaP, PC-3, PCAP-1, PTEN^−/−/p53^−/−, Caki

4T1 xenograft mice; A549 xenograft mice; B16F10 and MC38 xenograft mice; BxPC-3 xenograft mice; C26 xenograft mice; SKOV3 xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; enhances chemosensitivity; induces apoptosis, autophagy, cell cycle arrest; inhibits cell viability, survival

Activates caspase-3, -7, -8, -9, PARP, JNK pathway; Decreases mitochondrial membrane potential; Down-regulates Akt, ALDOA, ATG4B, Bcl-2, Bcl-xL, β-catenin, cFLIP_L, cyclin D1, DLL1, DLL3, DLL4, ERK, Jagged1, Jagged2, LRP, p-53, P-gp, Mcl-1, MMP-2, MMP-9, MRP2, PI3K, RRM2, SIRT1, survivin, TOPIIα, VEGF, XIAP; Enhances ROS accumulation, cytochrome c release; Inhibits ERK/E2F1/RRM2, MAPK, PI3K/Akt pathways, NF-κB p65 binding activity, Trx activity; Up-regulates AIF, Atg-5, Bax, CHOP, DUSP1, DUSP5, FoxO3a, c-Jun, p27, p53

200–400 nM; 0–1 μM; 0–2 μM; 0–3 μM; 0–5 μM; 0–8 μM; 0–10 μM; 0–40 μM; 0–50 μM; 0–51.8 μM; 0.5 µM; 0–3 μg/ml; 2 mg/kg; 8 mg/kg

Chlorochalcone; Cisplatin; Doxorubicin; 5–Fluorouracil; Gemcitabine; Nal¹³¹; Oxaliplatin; Retinoic acid; TRAIL

[639, 644, 646, 647, 650, 656, 657, 663,664,665, 953,954,955,956,957,958,959,960,961,962,963,964,965,966]

Artesunate

Artemisia annua L.

B-cell lymphoma; bladder cancer; breast cancer; colorectal cancer; gastric cancer; head and neck cancer; hepatocellular carcinoma; myelodysplastic syndrome; ovarian cancer; pancreatic cancer; prostate cancer; rhabdomyosarcoma

BL-41, Raji, Ramos, Rec-1, RT4, T24, ACHN, BT-474, MCF-7, MDA-MB-231, BGC-823, HGC-27, MGC-803, SGC-7901, HN3, HN4, HN9, SKM-1, HO8910, SKOV3, AsPC-1, BxPC-3, Colo-357, Panc-1, DU-145, LNCaP, RD18, TE671

BL-41 xenograft mice; A2780 xenograft mice; HO8910 xenograft mice; TE671 xenograft mice; MCF-7 xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; induces apoptosis, cell cycle arrest, DNA damage, ferroptosis

Activates caspase-3, -9, p38 MAPK pathway; Decreases metabolic capacity, mitochondrial membrane potential, PGE₂ production; Down-regulates Bcl-2, CDC25A, COX-2, cyclin B, cyclin D1, cyclin E2, γ-H2AX, IGF-1R, Keap1, c-Myc, PAX7, RAD51, STAT3, UCA1, xCT; Enhances ROS production; Up-regulates ATF-4, ATM, ATR, Bax, BRCA1, E-cadherin, CHK1, CHK2, CHOP, HO-1, microRNA-16, microRNA-133, microRNA-206, Nrf2, p53

0.1–10 μM; 0–50 μM; 0–100 μM; 0–120 μM; 0–200 μM; 50 μM; 0–50 μg/ml; 0–160 mg/L; 0–200 mg/kg; 50 mg/kg; 50, 150 mg/kg; 100 mg/kg; 200 mg/kg

Cisplatin; Connexin-43; Paclitaxel

[669, 673, 675, 681, 683, 688,689,690, 693, 695, 967,968,969,970,971]

Wogonin

Scutellaria baicalensis, Scutellaria amoena, Scutellaria rivularis, Anodendron affine Druce

Breast cancer; gastric cancer; head and neck cancer; hepatocellular carcinoma; leukemia; lymphoma; melanoma; multiple myeloma; neuroblastoma; osteosarcoma; ovarian cancer; pancreatic cancer; NSCLC

MDA-MB-231, BGC-823, MFC, MGC-803, MKN45, SGC-7901, AMC-HN2, AMC-HN3, AMC-HN4, AMC-HN5, AMC-HN9, AMC-HN4-cisR, AMC-HN9-cisR, SNU-1041, SNU-1066, SNU-1076, Bel-7402, Hep3B, HepG2, SMMC-7721, K562, K562/A02, K562R, Raji, B16F10, RPMI 8226, U266, IMR-32, SK-N-BE2, CD133⁺ CAL72, A549, A2780, Colo-357, Panc-1

MDA-MB-231 xenograft mice; Raji xenograft mice; AMC-HN4-cisR xenograft mice; AMC-HN9-cisR xenograft mice; B16F10 xenograft mice; BGC-823 xenograft mice and zebrafish; MFC xenograft mice; RPMI 8226 xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; induces apoptosis, autophagy, cell cycle arrest, ER stress, mitochondrial dysfunction; reverses drug resistance

Activates caspase-3, -4, -8, -9, -12, PARP, IRE1α-dependent pathway; Decreases mitochondrial membrane potential; Down-regulates Akt, B7H1, Bcl-2, CDK4, CDK6, cyclin D1, cyclin E, EGFR, ERK, HIF-1α, IL-8, IκB, IKKα, Ki-67, MMP-2, MMP-9, c-Myc, PDK1, PI3K, Rac1, RAE-1ε, SGK1, ULK1, VEGF; Enhances calreticulin, HMGB1, cytochrome c release, ROS accumulation; Inhibits 5-LO/BLT2/ERK/IL-8/MMP-9, NF-κB pathways; Up-regulates ASK, Bax, Bid, GRP78, GRP94, IRE1α, JNK, p21, p53, PU.1, PUMA

0–20 μM; 0–40 μM; 0–50 μM; 0–60 μM; 0–80 μM; 0–100 μM; 0–150 μM; 0–200 μM; 40 μM; 50 μM; 0–40 μg/ml; 0–60 mg/kg; 0–80 mg/kg; 8 mg/kg; 20 mg/kg; 60 mg/kg; 12.5 ng/zebrafish

Cisplatin; Paclitaxel; Oxaliplatin; Sorafenib

[704, 708, 709, 716, 717, 719, 721, 725, 730, 731, 741, 742, 972,973,974,975,976]

β-Elemene

Curcuma wenyujin Y. H. Chen et C. Ling, Rhizoma zedoariae, Curcuma Zedoary

Bladder cancer; bone neoplasms; breast cancer; cervical cancer; gastric cancer; melanoma; NSCLC; osteosarcoma; thyroid cancer

PBC, Bcap37, MBA-MD-231, MCF-7, MCF-7/ADR, MCF-7/DOC, 5637, SiHa, T-24, BGC-823, MKN45, SGC-7901, B16F10, A549, H358, H460, H1299, H1650, H1975, Lewis, PC9, MG63, U2OS, FTC-133

A549 xenograft mice; B16F10 xenograft mice; BGC-823 xenograft mice; Lewis tumor-bearing mice; MG63 xenograft mice; U2OS xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; enhances radiosensitivity; induces apoptosis, autophagy, cell cycle arrest; reverses chemoresistance

Activates caspase-3, -7, -8, -9, -10; Down-regulates Akt, Bcl-2, β-catenin, CDC25C, CDK1, cyclin B1, cyclin D1, endostatin, ERK, DNMT1, MMP-2, MMP-3, MMP-9, MTA3, c-Myc, STAT3, Sp1, survivin, TCF7, TIMP-1, TIMP-2, VEGF; Enhances ROS accumulation; Induces polarization from M2 to M1 macrophages; Inhibits Wnt/β-catenin pathway; Up-regulates ATF-4, ATF-6, Bad, Bax, BTF, CHK2, CHOP, FoxO3a, IGFBP1, IRE1α, p15, p21, p53, Pak1, PAK1IP1, PERK, TOPIIα

0–25 μM; 0–1000 μM; 67.5–1000 μM; 0–40 μg/ml; 0–50 μg/ml; 0–120 μg/ml; 0–160 μg/ml; 0–200 μg/ml; 0–320 μg/ml; 0–500 μg/ml; 0–800 μg/ml; 0–0.16 mg/ml; 15, 30 μg/ml; 100 mg/ml; 1 mg/kg; 20 mg/kg; 50 mg/kg; 75 mg/kg; 200 mg/kg

Cisplatin; Paclitaxel; Rapamycin

[746, 747, 749, 752, 754, 755, 762, 977,978,979,980,981,982,983,984,985,986,987]

Cepharanthine

Stephania cepharantha Hayata, Stephania japonica

Choroidal melanoma; colorectal cancer; breast cancer; gastric cancer; leukemia; nasopharyngeal carcinoma; NSCLC; ovarian cancer; renal carcinoma

MEL15-1, COLO-205, HCT-116 HT-29, SW-620, MCF-7, MDA-MB-231, Jurkat T-cells, A549, H1299, HCC827, NCI-H1299, NCI-H1650, NCI-H1975, CNE-1, CNE-2, A2780, A2780/Taxol, CaOV-3, OVCAR3, Caki

A549 xenograft mice; NCI-H1975 xenograft mice

Anti-angiogenesis; anti-metastasis; anti-proliferation; anti-tumor growth; induces apoptosis, autophagy, cell cycle arrest; Reverses multi-drug resistance

Activates caspase-3, -9, PARP; Decreases mitochondrial membrane potential; Down-regulates Akt, Bcl-2, Bcl-xL, CDK4, cyclin A, cyclin D, c-FLIP, mTOR, p50, p52, survivin; Enhances cytochrome c release, ROS accumulation; Inhibits lysosomal cathepsin B and cathepsin D maturation, Akt/mTOR, NF-κB, pathways; Up-regulates Atg-7, Bak, Bax, Beclin1, DR5, p38 MAPK, Mcl-1, p21^Waf1/Cip1, p53

0–15 μM; 0–20 μM; 0–80 μM; 0–100 μM; 0–120 μM; 2–8 μM; 4, 5 μM; 5–80 mM; 25 mg/kg; 50 mg/kg

Cisplatin; Dacomitinib; Paclitaxel; TRAIL

[777, 782,783,784,785,786,787,788,789,790, 794, 988]